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Juvenile harvest mice engaged in social play. The neural mechanisms underlying the encoding of social reward have remained unknown, despite the need for reinforcement of adaptive social interactions in order to keep such behaviours persistent throughout evolution. Here, Robert Malenka and colleagues report that, in the mouse nucleus accumbens core, the peptide hormone oxytocin is required both for social reinforcement and a form of presynaptic long-term depression of excitatory transmission onto medium spiny neurons. This social reinforcement signal could be disrupted if oxytocin receptors were specifically deleted from inputs arriving from the dorsal raphe nucleus, the major source of serotonin in the brain, or by blocking serotonergic receptors in the nucleus accumbens. Such coordinated activity between oxytocin and serotonin systems provides a possible mechanism for encoding social reinforcement and offers targets for studying further the neural mechanisms of social dysfunction. Cover: Jean-Louis Klein & Marie-Luce Hubert.
The effects of federal budget cuts provide an opportunity to revisit the funding structure of the National Institutes of Health, says Frederick Grinnell.
The week in science: Labour strike ends at ALMA observatory, NASA homes in on next Mars landing site, and Taiwan court clears environmental engineer of libel.
European collaboration is not far behind that in the United States, but there is still work to be done on cross-border funding and financial inequalities, says Paul Boyle.
A mathematical model of gun ownership has been developed that clarifies the debate on gun control and tentatively suggests that firearms restrictions may reduce the homicide rate.
A genome-wide screen of developing mouse embryos, performed using RNA-interference techniques, finds new suspects in skin cancer. But some factors seem to have opposing roles in cancer and normal-tissue maintenance. See Article p.185
A spectroscopic technique has been demonstrated that uses stimulated emission to enhance weak X-ray signals for fundamental studies in materials science. See Letter p.191
Host-cell detection of lipopolysaccharide in the outer membrane of Gram-negative bacteria was thought to be restricted to the cell-surface receptor TLR4. It emerges that lipopolysaccharide can also be sensed in the cytoplasm.
Fingerprints of sulphur isotopes in rocks from the ridge beneath the Atlantic Ocean suggest that a substantial fraction of sulphur at Earth's surface is left over from the formation of the planet's core. See Letter p.208
Cellular cross-talk, enzymatic catalysis and regulation of gene expression all depend on molecular recognition. A method that allows the design of proteins with desired recognition sites could thus be revolutionary. See Letter p.212
In male mice oxytocin acts as a social reinforcement signal within the nucleus accumbens (NAc) core, where it elicits a presynaptically expressed long-term depression (LTD) of excitatory synaptic transmission in medium spiny neurons; deletion of oxytocin receptors from the dorsal raphe nucleus, which provides serotonergic innervation of the NAc, and blockade of NAc serotonin 1B receptors both prevent oxytocin-induced LTD and social reward.
Here, the first genome-wide in vivo RNA interference screens in a mammalian animal model are reported: genes involved in normal and abnormal epithelial cell growth are studied in developing skin tissue in mouse embryos, and among the findings, β-catenin is shown to act as an antagonist to normal epithelial cell growth as well as promoting oncogene-driven growth.
Resonant inelastic X-ray scattering requires very high photon densities to detect the relatively weak signals of interest, but here it is demonstrated that inducing stimulated X-ray emission from crystalline silicon can increase the signal level by several orders of magnitude and reduces sample damage.
Tertiary alcohols are displaced with a nitrogen nucleophile with stereoinversion and with high selectivity over less substituted alcohols, providing complementarity to the SN2 reaction and efficient access to nitrogenous marine terpenoids.
Reconstructed changes in North Atlantic nitrogen fixation over the past 160,000 years have a 23,000-year cycle that is interpreted to result from precession-paced changes in the supply of phosphorus to surface waters by equatorial Atlantic upwelling.
Holocene aquifers are the source of much arsenic poisoning in south and southeast Asia, whereas Pleistocene aquifers are mostly safe; here the delayed arsenic contamination of a Pleistocene aquifer is described and modelled.
Earth’s mantle is shown to display heterogeneous sulphur isotope ratios, with a depleted end-member that is not chondritic as has been thought; the mantle’s inferred composition can be accounted for by fractionation during core–mantle differentiation.
Computational protein design is used to create a protein that binds the steroid digoxigenin (DIG) with high affinity and selectivity; the computational design methods described here should help to enable the development of a new generation of small molecule receptors for synthetic biology, diagnostics and therapeutics.
Exome sequencing has found an excess of de novo mutations in the ∼4,000 most intolerant genes in patients with two classical epileptic encephalopathies (infantile spasms and Lennox–Gastaut syndrome); among them are multiple de novo mutations in GABRB3 and ALG13.
Expression of the three transcription factors BLIMP1, PRDM14 and TFAP2C, or of PRDM14 alone, converts epiblast-like cells into primordial germ cell (PGC)-like cells; the transcription-factor-induced PGC-like cells acquire key transcriptome and epigenetic reprogramming in PGCs, and contribute to spermatogenesis and fertile offspring.
Using 4C technology, higher-order topological features of the pluripotent genome are identified; in pluripotent stem cells, Nanog clusters specifically with other pluripotency genes and this clustering is centred around Nanog-binding sites, suggesting that Nanog helps to shape the three-dimensional structure of the pluripotent genome and thereby contributes to the robustness of the pluripotent state.
The mechanism of action of three different allosteric MEK inhibitors that target the MAP kinase pathway is investigated, and their efficacy is shown to be explained by the distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours; this work provides a rationale for designing more effective cancer therapies for these common genetic subtypes of cancer.
The entire hepatitis C virus life cycle can be recapitulated in an inbred mouse model, allowing preclinical assessment of antiviral therapeutics and vaccines.
Several death-domain-containing proteins are directly inactivated by the enteropathogenic Escherichia coli type III secretion system effector NleB; NleB functions as an N-acetylglucosamine transferase that modifies a conserved death domain arginine residue, blocking the receptor–adapter interaction.
Colonizing enteric bacteria are shown to inhibit the antimicrobial process of host cell apoptosis through the action of NleB1, a type III secretion system effector with N-acetylglucosamine transferase activity, which can bind and modify eukaryotic death-domain-containing proteins.
Neuropilin-1 (Nrp1) on regulatory T (Treg) cells is shown to interact with semaphorin-4a (Sema4a) to promote a program of Treg-cell stability and survival, in part through PTEN-mediated modulation of Akt signalling; Nrp1-deficient Treg cells can maintain immune homeostasis but fail to suppress in inflammatory sites, such as tumours, providing an attractive immunotherapeutic target for the treatment of cancers.
The lipid-binding profiles of all lipid-transfer proteins in Saccharomyces cerevisiae are determined and a new subfamily of oxysterol-binding proteins that function in phosphatidylserine homeostasis and transport is identified.